Bacteria can exist as single entity as well as be part of a community of other bacteria (which could consist of same or different species of bacteria). In either lifestyle (free flowing or community), bacteria communicate with their neighbors via small molecules called autoinducers (a process called quorum sensing, QS). It is now appreciated that QS controls the expression of virulence factors or biofilm-associated genes in a variety of clinically important bacteria. AI-2 is termed a universal quorum sensing autoinducer and is used by a variety of bacteria, both pathogenic and human microbiota. Interception of AI-2 signaling with analogs at the synthesis level (LuxS), extracellular receptor (LuxP), transport of signal into bacteria (LuxB) have been proposed but compositions and methods for inhibition of AI-2 or processed AI-2 (such as phosphorylatedvAI-2) binding to intracellular receptors are poorly developed.
Bacteria that attach to surfaces can encase themselves in a self-synthesized hydrated matrix of polysaccharides and proteins to form slimy layers or biofilms. Biofilms mediate persistence and shield bacteria from hostile environments. These structured communities enable a multicellular existence that is distinct from planktonic forms. Biofilms are of high clinical relevance, as they exist in ˜80% of human infections. Pathogens in biofilms can exhibit antibiotic tolerance ˜1000 times higher than their planktonic counterparts. Antibiotic therapy, most effective against planktonic cells that slough off biofilms, is oftentimes unable to eradicate the biofilm itself. Thus, biofilm infections typically become chronic, leading to continual administration of antibiotics, which, in turn, contributes to the clinical challenge of antibiotic resistance. Further, modulation of specific bacteria, in the presence of other bacteria that also use AI-2 has been an unsolved challenge, and to date there has been no reported use of AI-2 antagonists to synergistically potentiate the activity of other antimicrobial agents.
Thus, there remains an ongoing and unmet need for new and improved compositions and methods for modulating the tactics that are used by bacteria that cause infection and/or undesirable biofilm formation. The present invention meets these and other needs.